Structures and functions of calcium channel beta subunits

Calcium channel beta subunits have profound effects on how alpha(1) subunits perform. In this article we summarize our present knowledge of the primary structures of beta subunits as deduced from cDNAs and illustrate their different properties. Upon co-expression with alpha(1) subunits, the effects of beta subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have different responses to voltage which are affected by beta subunits, such as lone-lasting prepulse facilitation of alpha(1C) (absent in alpha(1E)) and inhibition by G protein beta gamma dimer of alpha(1E), absent in alpha(1C). One beta subunit, a brain beta 2a splice variant that is palmitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of alpha(1) in oocytes requires a beta subunit even if the final channel shows no evidence for its presence. We propose two structural models for Ca2+ channels to account for "alpha(1) alone" channels seen in cells with limited beta subunit expression. In one model, beta dissociates from the mature alpha(1) after proper folding and membrane insertion. Regulated channels seen upon co-expression of high levels of beta would then have subunit composition alpha(1)beta In the other model, the "chaperoning" beta remains associated with the mature channel and "alpha(1) alone" channels would in fact be alpha(1)beta channels. Upon co-expression of high levels of beta the regulated channels would have composition [alpha(1)beta]beta.